The objective of the investigation is to enzymatically characterize the degradative pathway of the glycosaminoglucuronoglycan (acid mucopolysaccharide), dermatan sulfate. Mixed mucopolysaccharides labeled biosynthetically with a radioactive tracer are treated with a series of enzymes to leave dermatan sulfate as the only macromolecule. This serves as substrate for the examination of the degradation pathway. Enzymes thought to be necessary for hydrolyzing known constituents of the dermatan sulfate structure are isolated, each free from the others. The selection of enzymes is guided by recent discoveries on enzyme defects associated with the mucopolysaccharidoses. The ordered sequence of reactions for dermatan sulfate degradation will be mapped by employing enzymes in various sequences and combinations. It is expected that this will provide a model for the study of the breakdown of other mucopolysaccharide types. Mucopolysaccharide catabolism is involved in a wide spectrum of normal and pathological processes and these studies will be of value in several major areas of biomedical research including the genetic mucopolysaccharidoses, cystic fibrosis and rheumatoid arthritis. It is a truism that the elucidation of normal metabolic events must precede any real understanding of pathological conditions. Such knowledge should enhance the development of early diagnostic and form the basis for rational therapeutic and prophylactic treatment.